||Chronic kidney disease (CKD) is frequently associated with other chronic medical conditions. Adjusting for potential confounding factors that are associated with the outcome of interest is important both in clinical research and in everyday clinical practice. Comorbidity is such an important co-variable that it is reported to predict different outcomes in patients with ESRD. Health related quality of life (HRQoL) has increasingly been recognized as an important aspect of health care delivery, measure of effectiveness and patient experience, in chronic medical conditions. The progressively older ESRD patient population of industrialized countries is significantly debilitated by the burden of disease and also by the intrusiveness of renal replacement therapies. For these patients simply prolonging life is not enough. Little information has been published about the association of comorbidity and HRQoL. The aim of this review is to summarize the significance of comorbidity in patients with ESRD, with a special focus on the complex relationship between comorbidity and HRQoL. Several frequently used instruments will be described and the current literature, that compared the relative utility and accuracy of these tools, will be reviewed. Finally, the impact of selected medical conditions on HRQoL of patients with end-stage renal disease will be demonstrated.